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Biomedical subjects

G N Ling

Publications and source records attributed to G N Ling.

At least 37 records · Page 2Linked to original sources
PubMed1988

An electronic mechanism in the action of drugs, ATP, transmitters and other cardinal adsorbents. II. Effect of ouabain on the relative affinities for Li+, Na+, K+, and Rb+ of surface anionic sites that mediate the entry of Cs+ into frog ovarian eggs.

Ouabain enhanced the inhibitory effects of Li+, Na+, and K+ on the rate of Cs+ permeation into frog ovarian eggs while it reduced the inhibiting effect of Rb+. The data agree with earlier demonstrated effects of ouabain on the rank order of selective accumulation of the five alkali-metals in frog muscles and on the relative effectiveness of glycine, Li+, Na+, K+, Rb+, and Cs+ in inhibiting the rate of entry of Cs+ into frog sartorius muscle. In all three cases, the ouabain behaved as an electron-donating cardinal adsorbent (EDC) causing a rise of the electron density (c-value) of the beta- and gamma-carboxyl groups in the cell cytoplasm (for selective accumulation) and on the cell surface (for selective ion permeation). Explanations based on the association-induction hypothesis were offered why an EDC like ouabain does not initiate cell activation (like veratridine does) and why Ca++ and tetradotoxin delays or inhibits physiological and artificial cell activation.

Animals↗
PubMed1987

Studies on the physical state of water in living cells and model systems. VI. Concentration-dependent sustained volume changes of dialysis sacs containing aqueous solution of native and denatured protein, gelatin, and oxygen-containing polymers immersed in solutions of Na salt and of sugar and sugar alcohol.

In this paper we studied the volume changes of dialysis sacs containing concentrated solutions of native and denatured proteins and of oxygen-containing polymers after immersion in aqueous solution of Na-citrate, D-glucose, and sorbitol of varying concentration. The results confirm the theory of cell volume regulation: volume changes of living cells in different solutions represent a balance between the tendency of intracellular proteins -- which exist in the fully extended conformation -- to polarize, sorb, and draw into the sac or cell more water and the opposite tendency to lose water from the sac or cell created by the lower level of the solutes in the cell or sac water than in the external medium. The lower level of the solutes is the consequence of the reduced solvency of the polarized water in the sac or cell water for large and complex solutes like sugar and free amino acids. This study adds another important physico-chemical attribute of the living cell that can be duplicated by aqueous solutions of gelatin, oxygen-containing polymers like PEO and PEG as well as urea-denatured proteins but not, or only weakly so, by aqueous solutions of native proteins or SDS-denatured proteins.

Animals↗
PubMed1987

Studies on the physical state of water in living cells and model systems. VII. Exclusion of sugars and sugar alcohols from the water in sulfonate ion exchange resins: the "size rule".

The equilibrium distribution of D-arabinose, glycerol, D-ribose, sorbitol, sucrose or inulin in the water of sulfonate ion exchange resins (containing as counterions to the sulfonate anions, H+, Li+, Na+, K+, Rb+, Cs+, NH4+, tetraethylammonium or tetra-n-butyl-ammonium) was studied, usually at one temperature (25 degrees C) but sometimes at two (25 degrees C, 0 degrees C). The apparent equilibrium distribution (p-value) changes with the nature of the counterion, temperature and the molecular weights of the sugar, sugar alcohols, and derivative in question. Linear correlation coefficients between the molecular weights of the solutes and their respective p-values in the range of -0.92 to -0.93 were obtained when the resins were in the Li+, Na+, K+, or Rb+ form.

Anion Exchange Resins↗
PubMed1987

On the large error introduced in the estimate of the density of membrane pores from permeability measurements when diffusion in "unstirred layer" within the cells is disregarded.

After the development of the "black lipid membrane" techniques, studies of the permeability of labeled water and nonelectrolytes across these artificial membranes have yielded permeability constants comparable in magnitude to those obtained from tracer studies of living cell membranes. This general agreement has affirmed the belief that the living cell membranes are indeed closely similar to these bilayer phospholipid membranes. In this report, we draw attention to a hidden assumption behind such comparisons made: the assumption that labeled material passing through the cell membrane barriers instantly reaches diffusion equilibrium inside the cell. The permeability constants to labeled water (and nonelectrolytes) across lipid layers were obtained using setups in which the lipid membrane was sandwiched between aqueous compartments both of which were vigorously stirred. In studies of permeability of living cell membranes only the outside solution was stirred, the intracellular water remained stationary. Yet the calculations of permeability constants of the cell membrane were made with the tacit assumption, that once the labeled materials pass through the cell membrane, they were instantly mixed with the entire cell contents as if a stirrer operating at infinite speed had been present inside the cells. Ignoring this unstirred condition of the intracellular water, in fact, lumped all the real-life delay due to diffusion in the cytoplasm and added it to the resistance to diffusion of the membrane barrier. The result is an estimated membrane permeability to labeled water (and nonelectrolytes) many times slower than it actually is. The present report begins with a detailed analysis of a specific case: tritiated water diffusion from giant barnacle muscle fibers and two non-living models, one real, one imagined.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Membrane↗
PubMed1987

Cell volumes and water contents of frog muscles in solutions of permeant sugars and sugar alcohols.

1. Previous work has suggested that living cells may acquire and then maintain different water contents and hence volume, in solutions containing different concentrations of solutes that are permeant to the cell membrane. Toward better understanding of this phenomenon, two hypotheses were introduced: one hypothesis is based on the membrane-pump theory; another represents an extension of the polarized multilayer theory of cell water, a part of the association-induction (AI) hypothesis. To test the different predictions of these hypotheses, the water contents of frog muscle equilibrated at 25 degrees C in solutions of different concentrations of seven pentoses, seven hexoses, seven dissacharides, two trisaccharides, and six sugar alcohols were determined. 2. The earlier finding of sustained shrinkage of muscle cells in concentrated solutions of permeant solutes was confirmed once more. 3. In equimolal solutions of sugars and sugar alcohols with different steric conformations but the same or closely similar molecular weight(s), muscles had the same or closely similar water content(s). 4. In equimolal solutions of different sugars and sugar alcohols, the equilibrium water contents of the muscles increased with decreasing molecular weights of these solutes. 5. The water contents of muscles, equilibrated in 0.4 M solutions of different sugars and sugar alcohols, are positively correlated with the equilibrium distribution coefficients (or q-values) of the sugar and sugar alcohols in the muscle cell water with a linear correlation coefficient of +0.973. 6. The relationships between the equilibrium water contents of muscles (in solutions containing different concentrations of different sugars and sugar alcohols) and the concentrations of these sugars and sugar alcohols agree in general contours with that predicted by an equation derived on the basis of the polarized multilayer theory of cell water. 7. The experimental findings described above do not agree with the prediction based on the membrane-pump hypothesis; they do agree with all four predictions of the hypothesis based on the polarized multilayer theory of cell water.

Animals↗
PubMed1987

An electronic mechanism in the actions of drugs and other cardinal adsorbents. I. Effects of ouabain on the relative affinities of the cell surface beta- and gamma-carboxyl groups for K+, Na+, glycine and other ions.

The effects of ouabain on the effectiveness of glycine, Li+, Na+, K+, Rb+, and Cs+ in the external medium in reducing the rate of entry of labeled Cs+ into frog sartorius muscles were studied. The results showed that in the absence of ouabain the effectiveness of glycine and alkali-metal ions in inhibiting labeled Cs+ entry follows the rank order: K+ greater than Cs+, Rb+ greater than Na+, Li+ greater than glycine. Exposure to ouabain in essence reverses this order which then becomes: glycine greater than Li+, Na+ greater than K+, Rb+, greater than Cs+. These results confirm the prediction of the basic electronic interpretation of drug action according to the association-induction hypothesis. In addition, it shows that the action of ouabain on the surface beta- and gamma-carboxyl groups of frog muscle mediating Cs+ entry is quite similar to its action on the cytoplasmic beta- and gamma-carboxyl groups that are the seats of K+ accumulation in the bulk phase cytoplasm as well as to its action on the cell surface beta- and gamma-carboxyl groups responsible for the generation of the resting potential. In all these cases, ouabain acts as an electron-donating cardinal adsorbent (EDC). Finally the marked increase of the binding strength of glycine on the surface beta- and gamma-carboxyl groups was used to explain the primary pharmacodynamic effect of cardiac glycosides in combating heart failure.

Adsorption↗
PubMed1986

Membrane lipid layers vs. polarized water dominated by fixed ions: a comparative study of the effects of three macrocyclic ionophores on the K+ permeability of frog skeletal muscle, frog ovarian eggs, and human erythrocytes.

The effects of 10(-7) M valinomycin, nonactin, and monactin on human erythrocytes, frog sartorius muscle, and frog ovarian oocytes in the presence of varying external K+ concentration were studied. The results showed essentially a consistent but relatively modest increase of the K+ permeability constant in cm/sec with all three antibiotics on human erythrocytes. No change in response to any one of the antibiotics was observed in frog muscles or in frog ovarian eggs. These results and reports of similar failure to demonstrate ionophore-mediated increase of K+ permeability in squid axon and inner membrane of the liver mitochondria led to the conclusion that lipid membrane barrier to ionic traffic may be significant in the human erythrocytes but even here one must regard the evidence as tentative. In contrast, for the majority of other cell types studied, the data indicate the primary, if not exclusive route of ion traffic, is via the nonlipid component of the cell membrane. The evidence that these nonlipid paths are the fixed charge-polarized water layer complex and that they cover much of the cell surface of many types of living cells was discussed.

Animals↗
PubMed1986

Cooperative interaction among surface beta- and gamma-carboxyl groups mediating the permeation of ions into frog muscle cells.

A new equation for the ion permeation into living cells is described. This equation, differs from earlier ones, in that cooperative interaction among the fixed surface beta- and gamma-carboxyl groups mediating ion entry via the adsorption-desorption route is taken into account. Results of a single set of experiments describing labeled Cs+ into frog sartorius muscles at 0 degree C affirms the existence of the predicted cooperative interaction which endows the cell membrane and other organelles with a mechanism for coherence and control.

Animals↗
PubMed1986

The role of inductive effect in the determination of protein structure.

The inductive theory, formally introduced by G. N. Lewis has thus far found its major applications in interpreting and predicting equilibrium and kinetic properties of small organic molecules. Evidence is presented demonstrating that the inductive effect can also help to explain the determination of protein structure by its amino acid sequence. Suggestions are also made that the inductive effect plays a significant role in protein conformation changes brought about by ligand binding.

Amino Acid Sequence↗
PubMed1984

Counterarguments against alleged proof of the NA-K pump in studies of K+ and Na+ distributions in amphibian eggs.

With the aid of an ingenious technique called the reference phase method, Horowitz and his coworkers tested the alternative theories of solute distribution in living cells. Many interesting and significant findings were reported. However, a careful study of their papers led me to the belief that their claim of a proof for the Na pump theory was unwarranted. By taking into account other relevant information in the literature one can argue that their data in fact support an alternative hypothesis, the association-induction hypothesis.

Adsorption↗
PubMed1984

Warming-induced hyperpolarization of cardiac muscle cells and snail neurones: interpretation based on temperature transition of cooperatively linked surface anionic sites between K+ and Na+ adsorbing states.

The resting potential of a variety of living cells exhibits pronounced hyperpolarization when the cooled cells are brought to a higher temperature. It was shown that this phenomenon can be quantitatively described by the surface adsorption theory of the cell electrical potential in terms of a cooperative temperature transition of the protein-ion-water system at the cell surface. As such, the basic mechanism resembles the temperature transition demonstrated for the bulk phase K+-Na+ distribution in these and similar cells. The paper also discusses the resting potentials of frog muscles and squid axons which do not exhibit hyperpolarization on warming.

Animals↗
PubMed1984

A study of selective adsorption of Na+ and other alkali-metal ions on isolated proteins: a test of the salt-linkage hypothesis.

According to the salt-linkage hypothesis (a part of the association-induction hypothesis), the binding of alkali-metal ions on isolated proteins may be low as a result of the masking of cation-binding fixed anionic groups by the formation of "salt linkages" between them and fixed cationic groups. This hypothesis has been verified in a quantitative manner by the measurement of free and adsorbed Na+ in solutions of bovine hemoglobin titrated with increasing concentration of NaOH. In addition this communication presents data indicating (1) wide variability in the extent of Na+ adsorption among different isolated proteins and even among different samples of the same protein, (2) auto-cooperativity in the pH titration and Na+ adsorption, and (3) selectivity of the liberated fixed anionic groups for different alkali-metal ions in the rank order Na greater than Li greater than K greater than Rb, Cs.

Adsorption↗
PubMed1984

Quantitative relationships between the concentration of proteins and the concentration of K+ and Na+ in red cell ghosts.

The concentration of K+ accumulated in and Na+ extruded from red blood cell ghosts are quantitatively correlated with the total protein contents of the ghosts with a linear correlation coefficient of +0.80. The straight line derived from the 43 sets of data on K+ accumulated in the presence of varying ghost proteins, when extrapolated to the protein content of a normal red blood cell, yields a total K+ content close to that actually found in normal red blood cells. This quantitative relationship agrees with the prediction of the AI hypothesis that there should be a stoichiometric relation between the K-adsorbing protein(s) and the concentration of K+ accumulated. In addition the data suggests that in red blood cells the protein providing most of the K+ adsorbing sites is hemoglobin. The apparent equilibrium distribution coefficient, or p-value, of Na+ dissolved in the ghost water at different protein concentrations and in intact red blood cells follows a pattern similar to that seen in solutions of gelatin and of oxygen-containing linear polymers.

Blood Proteins↗
PubMed1984

Effects of adrenaline, calcium, and ouabain on the resting potential of frog muscle: interpretation based on the theory of allosteric control of cooperative interactions among surface anionic sites.

The surface adsorption theory of the cellular electric potential, a subsidiary of the association-induction hypothesis, can offer quantitative interpretations of the equilibrium resting potential of frog muscle in the presence of a constant concentration (100 mM) of external Na+ and varying external K+ (ranging from 0.1 mM to 100 mM) both in the absence and in the presence of cardinal adsorbents (ouabain, adrenaline, or Ca++). The theory can also quantitatively describe experimental data published by other laboratories from the studies of various cell types in the presence of these and other cardinal adsorbents, including some well known data which, up to now, have been regarded as specific evidence in support of the electrogenic pump theory.

Animals↗